NOVEL EXTRACELLULAR PROTEINS IN AXON GUIDANCE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们神经系统的细胞相隔很远，必须通过能够传输电信号或化学信号的线路相互连接。这些单独的纤维被称为轴突，在早期胚胎中，它们必须经过很长的距离才能连接神经系统。细胞通过它们表面的蛋白质来感知环境，这种蛋白质被称为受体，它绑定了环境中的信号。目前已知的轴突信号和受体很少。一类是Netrin蛋白家族，它刺激发育中的脊髓中的生长神经，以及包括血管在内的其他类型的细胞。通过遗传筛选，我们已经确定了一种新的Netrin蛋白受体，唐氏综合症细胞黏附分子(DSCAM)。在唐氏综合症患者中，有一份额外的21号染色体拷贝。尽管21号染色体上有数百个基因，但只有几个基因被认为是导致大多数症状的原因。其中一个基因是Dscam，一种细胞黏附分子，它允许细胞相互黏附。基德博士的研究表明，Dscam作为Netrin受体发挥作用，在神经和细胞迁移时引导它们。DSCAM似乎也是在发育中的神经系统中发挥作用的尚未确定的信号的受体。这增加了我们对脊髓和大脑如何形成的理解，以及对脊髓损伤的影响，以及其他影响神经和血管的疾病，如糖尿病。了解DSCAM既是一种细胞黏附分子又是一种受体，应该可以更好地了解唐氏综合症的表型是如何发展的，包括在患者中常见的先天性心脏病。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The cells of our nervous system are separated by large distances and must be connected to one another by wiring capable of carrying electrical or chemical signals. The individual fibers are known as axons, and in the early embryo they have to navigate large distances to connect up the nervous system. Cells sense their environment through proteins, known as receptors, on their surfaces that bind signals in their environment. Few signals and receptors for axons are currently known. One class is the Netrin protein family that stimulates growing nerves in the developing spinal cord, as well as other cell types including blood vessels. Through genetic screens, we have identified a novel receptor for Netrin proteins, the Down Syndrome Cell Adhesion Molecule (Dscam). In Down syndrome patients, there is an extra copy of chromosome 21. Although there are several hundred genes on chromosome 21, only a few of those genes are thought to be responsible for the majority of the symptoms. One of these genes is Dscam, a cell adhesion molecule, which allows cells to stick to one another. Dr. Kidd's work has shown that Dscam functions as a Netrin receptor to guide both nerves and cells as they migrate. Dscam also appears to be a receptor for yet to be identified cues that function in the developing nervous system. This adds to our understanding of how spinal cords and brains form, as well as having implications for spinal cord injury, as well as other conditions that impact both nerves and blood vessels such as diabetes. Knowledge that Dscam functions as both a cell adhesion molecule and as a receptor should allow for a greater understanding of how the Down Syndrome phenotype develops, including the congenital heart disease frequently seen in patients.